ESRRB

estrogen related receptor beta, the group of Estrogen related receptors

Basic information

Region (hg38): 14:76310712-76501837

Previous symbols: [ "ESRL2", "DFNB35" ]

Links

ENSG00000119715 ∙ NCBI:2103 ∙ OMIM:602167 ∙ HGNC:3473 ∙ Uniprot:O95718 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 35 (Strong), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 35 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 35	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	12529709; 18179891; 26805784

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ESRRB gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ESRRB gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	27	2	33
missense		1	67	6	1	75
nonsense	1	4				5
start loss						0
frameshift		4	2			6
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region			3	1		4
non coding			34	36	24	94
Total	1	11	107	69	27

Variants in ESRRB

This is a list of pathogenic ClinVar variants found in the ESRRB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-76371349-G-A		Autosomal recessive nonsyndromic hearing loss 35	Uncertain significance (Jan 12, 2018)
14-76371394-G-A		Autosomal recessive nonsyndromic hearing loss 35	Uncertain significance (Jan 12, 2018)
14-76371418-A-G		Autosomal recessive nonsyndromic hearing loss 35	Uncertain significance (Jan 12, 2018)
14-76371426-C-A		Autosomal recessive nonsyndromic hearing loss 35	Uncertain significance (Jan 13, 2018)
14-76371482-C-T		Autosomal recessive nonsyndromic hearing loss 35	Uncertain significance (Jan 13, 2018)
14-76371507-A-G		Autosomal recessive nonsyndromic hearing loss 35	Uncertain significance (Jan 13, 2018)
14-76371527-T-C		Autosomal recessive nonsyndromic hearing loss 35	Uncertain significance (Jan 13, 2018)
14-76404414-T-C		Autosomal recessive nonsyndromic hearing loss 35	Uncertain significance (Jan 12, 2018)
14-76404419-G-A		Autosomal recessive nonsyndromic hearing loss 35	Uncertain significance (Apr 27, 2017)
14-76404456-T-C		Autosomal recessive nonsyndromic hearing loss 35	Uncertain significance (Mar 02, 2018)
14-76439036-C-T			Likely benign (Dec 12, 2018)
14-76439323-C-T			Likely benign (Jun 17, 2021)
14-76439356-G-A		Premature ovarian insufficiency	Uncertain significance (Jan 10, 2018)
14-76439365-C-A			Uncertain significance (Jul 11, 2018)
14-76439369-A-G		not specified • Autosomal recessive nonsyndromic hearing loss 35	Benign (Dec 12, 2023)
14-76439428-G-A			Likely benign (Feb 21, 2022)
14-76439434-C-A		not specified • Autosomal recessive nonsyndromic hearing loss 35	Benign (Jan 31, 2024)
14-76439467-G-A		Autosomal recessive nonsyndromic hearing loss 35 • not specified	Conflicting classifications of pathogenicity (Dec 10, 2023)
14-76439474-G-A		not specified	Uncertain significance (Jul 05, 2022)
14-76439480-G-A		Autosomal recessive nonsyndromic hearing loss 35	Uncertain significance (Apr 25, 2024)
14-76439494-G-C		not specified • Autosomal recessive nonsyndromic hearing loss 35	Benign/Likely benign (Jan 18, 2024)
14-76439496-C-T		not specified • Autosomal recessive nonsyndromic hearing loss 35 • ESRRB-related disorder	Conflicting classifications of pathogenicity (Oct 22, 2023)
14-76439511-C-T		not specified	Uncertain significance (Nov 15, 2021)
14-76439515-C-T			Likely benign (Mar 31, 2023)
14-76439516-G-A		Autosomal recessive nonsyndromic hearing loss 35	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ESRRB	protein_coding	protein_coding	ENST00000380887	8	191222

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.126	0.874	125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.56	229	306	0.749	0.0000201	3270
Missense in Polyphen		61	109.01	0.55956		1167
Synonymous	0.628	129	138	0.932	0.0000106	1022
Loss of Function	3.26	6	22.8	0.263	0.00000123	250

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000495	0.000495
Ashkenazi Jewish	0.00	0.00
East Asian	0.000113	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000472	0.0000439
Middle Eastern	0.000113	0.000109
South Asian	0.0000327	0.0000327
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 3: Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcription activity (PubMed:17920186, PubMed:19755138). Plays a role, in a LIF-independent manner, in maintainance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF signaling pathway and Wnt signaling pathways. Upon FGF signaling pathway activation, interacts with KDM1A by directly binding to enhancer site of ELF5 and EOMES and activating their transcription leading to self-renewal of trophoblast stem cells. Also regulates expression of multiple rod-specific genes and is required for survival of this cell type (By similarity). Plays a role as transcription factor activator of GATA6, NR0B1, POU5F1 and PERM1 (PubMed:23836911). Plays a role as transcription factor repressor of NFE2L2 transcriptional activity and ESR1 transcriptional activity (PubMed:17920186, PubMed:19755138). During mitosis remains bound to a subset of interphase target genes, including pluripotency regulators, through the canonical ESRRB recognition (ERRE) sequence, leading to their transcriptional activation in early G1 phase. Can coassemble on structured DNA elements with other transcription factors like SOX2, POU5F1, KDM1A and NCOA3 to trigger ESRRB-dependent gene activation. This mechanism, in the case of SOX2 corecruitment prevents the embryonic stem cells (ESCs) to epiblast stem cells (EpiSC) transition through positive regulation of NR0B1 that inhibits the EpiSC transcriptional program. Also plays a role inner ear development by controlling expression of ion channels and transporters and in early placentation (By similarity). {ECO:0000250|UniProtKB:Q61539, ECO:0000269|PubMed:17920186, ECO:0000269|PubMed:19755138, ECO:0000269|PubMed:23836911}.
• Disease: DISEASE: Deafness, autosomal recessive, 35 (DFNB35) [MIM:608565]: A form of non-syndromic deafness characterized by non-progressive, prelingual hearing loss. {ECO:0000269|PubMed:18179891}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);NHR;Nuclear Receptors;Wnt Signaling Pathway and Pluripotency;Gene expression (Transcription);Generic Transcription Pathway;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription (Consensus)

Recessive Scores

• pRec: 0.203

Intolerance Scores

• loftool: 0.193
• rvis_EVS: 0.18
• rvis_percentile_EVS: 66.07

Haploinsufficiency Scores

• pHI: 0.187
• hipred: Y
• hipred_score: 0.809
• ghis: 0.440

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.966

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Esrrb
• Phenotype: muscle phenotype; growth/size/body region phenotype; embryo phenotype; hearing/vestibular/ear phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: embryonic placenta development;regulation of transcription, DNA-templated;transcription initiation from RNA polymerase II promoter;stem cell division;stem cell population maintenance;intracellular receptor signaling pathway;steroid hormone mediated signaling pathway;cell dedifferentiation;photoreceptor cell maintenance;positive regulation of glycogen biosynthetic process;positive regulation of glycolytic process;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;inner ear development;positive regulation of transcription involved in G1/S transition of mitotic cell cycle;positive regulation of transcription involved in G2/M transition of mitotic cell cycle;positive regulation of stem cell population maintenance;regulation of stem cell division;negative regulation of stem cell differentiation
• Cellular component: condensed chromosome;nucleus;nucleoplasm;cytoplasm;integrator complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II complex binding;enhancer sequence-specific DNA binding;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;steroid hormone receptor activity;nuclear receptor activity;steroid binding;transcription factor binding;zinc ion binding;sequence-specific DNA binding